title: Antiflammin-1 attenuates bleomycin-induced pulmonary fibrosis in mice.
abstract: BACKGROUND
  Antiflammin-1 (AF-1), a derivative of uteroglobin (UG), is a synthetic nonapeptide with diverse biological functions. In the present study, we investigated whether AF-1 has a protective effect against bleomycin-induced pulmonary fibrosis.
  
  
  METHODS
  C57BL/6 mice were injected with bleomycin intratracheally to create an animal model of bleomycin-induced pulmonary fibrosis. On Day 7 and Day 28, we examined the anti-inflammatory effect and antifibrotic effect, respectively, of AF-1 on the bleomycin-treated mice. The effects of AF-1 on the transforming growth factor-beta 1 (TGF-β1)-induced proliferation of murine lung fibroblasts (NIH3T3) were examined by a bromodeoxycytidine (BrdU) incorporation assay and cell cycle analysis.
  
  
  RESULTS
  Severe lung inflammation and fibrosis were observed in the bleomycin-treated mice on Day 7 and Day 28, respectively. Administration of AF-1 significantly reduced the number of neutrophils in the bronchoalveolar lavage fluid (BALF) and the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in the lung homogenates on Day 7. Histological examination revealed that AF-1 markedly reduced the number of infiltrating cells on Day 7 and attenuated the collagen deposition and destruction of lung architecture on Day 28. The hydroxyproline (HYP) content was significantly decreased in the AF-1-treated mice. In vitro, AF-1 inhibited the TGF-β1-induced proliferation of NIH3T3 cells, which was mediated by the UG receptor.
  
  
  CONCLUSIONS
  AF-1 has anti-inflammatory and antifibrotic actions in bleomycin-induced lung injury. We propose that the antifibrotic effect of AF-1 might be related to its suppression of fibroblast growth in bleomycin-treated lungs and that AF-1 has potential as a new therapeutic tool for pulmonary fibrosis.
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha 410078, PR China. luozq1962@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Wan
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Han
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Feng
authors.forename: Shao-Jie
authors.initials: SJ
authors.lastname: Yue
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Qing-Mei
authors.initials: QM
authors.lastname: Cheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Zi-Qiang
authors.initials: ZQ
authors.lastname: Luo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014598:Uteroglobin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D010446:Peptide Fragments; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; C064645:antiflammin P1; D014598:Uteroglobin; D006909:Hydroxyproline